Genistein ameliorates parathyroid hormone-induced epithelial-to-mesenchymal transition and inhibits expression of connective tissue growth factor in human renal proximal tubular cells.
Genistein ameliorates parathyroid hormone-induced epithelial-to-mesenchymal transition and inhibits expression of connective tissue growth factor in human renal proximal tubular cells.
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DOI：
10.5114/aoms.2013.36929
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发表时间：
2013-08-30
期刊：
影响因子：
--
通讯作者：
Yuan W
中科院分区：
文献类型：
--
作者：
Guo Y;Zhang A;Ding Y;Wang Y;Yuan W
染料木黄酮是一种大豆和大豆制品，据报道可以抑制多种癌细胞的生长，但没有证据表明它可以治疗慢性肾脏疾病。目的是研究染料木素是否有抑制甲状旁腺激素（PTH）诱导的肾间质纤维化的潜力。采用免疫荧光法检测人肾小管上皮HK-2细胞α-平滑肌肌动蛋白（α-SMA）水平。Western blot检测α-平滑肌肌动蛋白、E-cadherin、结缔组织生长因子（CTGF）水平。用荧光素酶报告基因法检测CTGF基因的启动子活性。PTH （0.1 nM）作用48 h后，显著诱导细胞α-SMA蛋白表达，E-cadherin蛋白表达显著降低，CTGF基因启动子活性及其mRNA和蛋白表达水平升高（p < 0.01）。有趣的是，染料木素有效抑制pth诱导的α-SMA表达，恢复E-cadherin表达，降低CTGF mRNA和蛋白表达，并以剂量依赖性方式抑制CTGF启动子活性。染料木素能够阻断PTH治疗后肾转分化和上皮-间质转化的生物标志物α-SMA，抑制人肾小管上皮细胞中CTGF的表达；这些可能是染料木素抗纤维化作用的重要作用模式，可能对其在肾间质纤维化的临床治疗中具有重要意义。
Genistein, a soybean and soy-based product, has been reported to inhibit the growth of a wide range of cancer cells, but there is no evidence concerning its treatment of chronic kidney disease. The aim was to investigate whether genistein has potential to inhibit parathyroid hormone (PTH)-induced renal interstitial fibrosis. Using human renal tubular epithelial HK-2 cells, α-smooth muscle actin (α-SMA) was assessed by using immunofluorescence detection. α-Smooth muscle actin, E-cadherin and connective tissue growth factor (CTGF) were measured by Western blot analysis. The promoter activity of the CTGF gene was examined by the luciferase reporter assay. When cells were treated with PTH (0.1 nM) for 48 h, α-SMA protein expression was induced significantly, the protein expression of E-cadherin decreased substantially, and the promoter activity of the CTGF gene as well as its mRNA and protein expression levels increased (p < 0.01). Interestingly, genistein effectively inhibited PTH-induced α-SMA expression, restored E-cadherin expression, decreased mRNA and protein expression of CTGF, and suppressed the promoter activity of CTGF in a dose-dependent manner. Genistein has the ability to block the biomarker for renal transdifferentiation and epithelial-to-mesenchymal transition, α-SMA, following PTH treatment and inhibit CTGF expression in human renal tubular epithelial cells; these might be important modes of actions that contribute to genistein anti-fibrogenic effects and may have great implications for its potential in clinical treatment of renal interstitial fibrosis.
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影响因子：
6.7
作者：
Verdrengh, M;Jonsson, IM;Tarkowski, A
通讯作者：
Tarkowski, A
DOI：
10.1083/jcb.130.2.393
发表时间：
1995-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Strutz F;Okada H;Lo CW;Danoff T;Carone RL;Tomaszewski JE;Neilson EG
通讯作者：
Neilson EG
影响因子：
19.6
作者：
Ito, Y;Aten, J;Goldschmeding, R
通讯作者：
Goldschmeding, R
影响因子：
3.1
作者：
Piotrowska, Ewa;Jakobkiewicz-Banecka, Joanna;Wegrzyn, Grzegorz
通讯作者：
Wegrzyn, Grzegorz
影响因子：
1.3
作者：
Yuan, Wei-Jie;Jia, Feng-Yu;Meng, Jian-Zhong
通讯作者：
Meng, Jian-Zhong